Group Of Neutrophilic Dermatoses Research Articles

Pyoderma Gangrenosum: An Updated Literature Review on Established and Emerging Pharmacological Treatments

Pyoderma gangrenosum is a rare inflammatory skin disease classified within the group of neutrophilic dermatoses and clinically characterized by painful, rapidly evolving cutaneous ulcers with undermined, irregular, erythematous-violaceous edges. Pyoderma gangrenosum pathogenesis is complex and involves a profound dysregulation of components of both innate and adaptive immunity in genetically predisposed individuals, with the follicular unit increasingly recognized as the putative initial target. T helper 17/T helper 1-skewed inflammation and exaggerated inflammasome activation lead to a dysregulated neutrophil-dominant milieu with high levels of tumor necrosis factor-α, interleukin (IL)-1β, IL-1α, IL-8, IL-12, IL-15, IL-17, IL-23, and IL-36. Low-evidence studies and a lack of validated diagnostic and response criteria have hindered the discovery and validation of new effective treatments for pyoderma gangrenosum. We review established and emerging treatments for pyoderma gangrenosum. A therapeutic algorithm based on available evidence is also provided. For emerging treatments, we review target molecules and their role in the pathogenesis of pyoderma gangrenosum.

Seltene Erkrankungen an der Haut erkennen

The correct interpretation of skin manifestations can facilitate the diagnosis of many rare systemic diseases. Such manifestations can be due to autoimmune diseases (e.g. dermatomyositis, systemic lupus erythematosus, systemic sclerosis and sarcoidosis) and metabolic diseases (e.g. Anderson-Fabry disease and porphyria cutanea tarda). Other cutaneous symptoms are of great importance because they are possible warning signs of occult diseases of internal organs. This is true for example for some diseases from the group of neutrophilic dermatoses, such as Sweet's syndrome and pyoderma gangraenosum.

T helper type 1-related molecules as well as interleukin-15 are hyperexpressed in the skin lesions of patients with pyoderma gangrenosum.

Pyoderma gangrenosum (PG) is a rare, immune-mediated skin disease classified into the group of neutrophilic dermatoses. Although a number of studies confirmed the central role of innate immunity, only few studies have investigated the possible contributing role of acquired immunity. In particular, no reports concerning T helper type 1 (Th1) and Th2 cells are available as yet. Therefore, 15 patients with PG, five with Sweet's syndrome (SS) and nine skin specimens from healthy controls (HC) were investigated, evaluating the expression of Th1-related markers interleukin (IL)-12, interferon (IFN)-γ, C-X-C motif chemokine receptor 3 (CXCR3) and C-C motif chemokine receptor 5 (CCR5), of the Th2-related molecules IL-4, IL-5, IL-13 and CCR3, of the co-stimulatory axis CD40/CD40 ligand, of IL-15 and the natural killer (NK) cell marker CD56 in skin lesions by immunohistochemistry. Patients with PG and SS showed a higher expression of Th1 markers than HC. Conversely, IL-5- and CCR3-expressing cells were less numerous in PG skin lesions compared to SS (P = 0·0157 and <0·0001, respectively). Both CD40 and CD40L were expressed more in PG than in SS and HC (P < 0·0001 for both). Finally, the number of IL-15+ and CD56+ cells was higher in the skin of patients with PG than in those of SS and HC (P < 0·0001 for both). Our results suggest that Th2 cells are down-regulated in PG. At the same time, over-expression of the co-stimulatory axis CD40/CD40L amplifies the impairment of the Th1/Th2 balance. Both these findings might explain the most aggressive behaviour of PG in comparison to SS. Moreover, over-expression of IL-15+ and CD56+ cells may suggest a possible role of NK cells in the pathogenesis of the disease.

Pyoderma Gangrenosum Vegetans

Pyoderma Vegetans (PV) is a chronic inflammatory disease that usually presents as verrucose plaques. It belongs to the group of neutrophilic dermatoses and it is diagnosed right after other inflammatory and infectious diseases are excluded. It shows no association to systemic disorders and has great response to oral corticosteroids. We hereby report a patient presenting PV of lower limbs.

[The modern concepts of pyoderma gangrenosum].

The review provides an update on pyoderma ganrenosum, a rare chronic disease from a group of neutrophilic dermatoses. It considers its pathogenesis, its association with background visceral disease, and the specific features of skin and visceral involvement. Major and minor diagnostic criteria and differential treatment approaches are given.

Dermo-hypodermites nécrosantes neutrophiliques postopératoires de la main. Un diagnostic à ne pas rater

Pyoderma gangrenosum (PG) is an aseptic ulcerative dermatosis, belonging to the group of neutrophilic dermatoses, and could reveal a systemic blood disorders or inflammatory disease. This dermatosis could mimic rapidly extensive necrotizing dermo-hypodermitis in some clinical aspects. PG can be caused by tissue trauma as in surgical procedure. In this context, this pathology is easily confused with bacterial necrotizing dermo-hypodermitis, the treatment of which gives priority to survival rather than functional outcome, and causes rapid deterioration especially in the upper limb. This case report shows typical evolution of inappropriate treatment of postoperative PG. Faced with postoperative necrotizing dermo-hypodermitis, the diagnosis of PG must be considered, in order to favor good functional outcome.

Erythema elevatum et diutinum assoziiert mit pulmonalen Infiltraten und nekrotisierender Keratopathie – eine diagnostische Herausforderung!

Erythema elevatum et diutinum (EED) is subsumed in the group of neutrophilic dermatoses. Histological features display a leucocytoclastic vasculitis in early stages and concentric fibrosis in late stages of the disease. Associations to necrotizing pulmonary infiltrates or oculopathies are known. Co-incidence of an EED with necrotizing keratopathia and necrotizing bilateral pulmonary lesions has not been described yet.

Sweet’s syndrome and erythema nodosum: two neutrophilic dermatoses?

Dear Editor, We have read with great interest the article by Wasson and Folzenlogen about the concurrent occurrence of Sweet’s syndrome (SS) and erythema nodosum (EN) [1]. We would like to state some observations about this article. We entirely agree that SS and EN share some features that closely link these two reactive dermatoses: inflammatory clinical picture with acute onset, common associated conditions as inflammatory bowel disease or streptococcal infection and response to similar therapeutic agents as systemic glucocorticoids or potassium iodide. Moreover, although EN is not considered as neutrophilic dermatosis, many cases of this condition can show, especially in their initial phases, a neutrophil-rich infiltrate [2–4]. These coincidences are additionally supported by the report of many patients with both conditions, not only concurrently, as it is usual, but also successively: there are patients who can react to the same stimulus sometimes with SS and sometimes with EN [5, 6]. All of these data support our conviction that EN could be included within the group of the neutrophilic dermatoses. In addition to the case reports about the association of SS and EN cited by Wasson and Folzenlogen, there are several case series of SS that show the association between these two dermatoses and, unlike that it is asseverated by those authors, these associations are supported by histopathological studies. In our case series of 16 patients with SS, 5 of them (31%) presented a biopsy-proven EN [7]. There also are at least two other case series of patients with SS showing biopsy-proven EN: Vanaclocha [8] and Sitjas et al. [9] reported that 25% and 30% of their patients with SS had EN, respectively. These studies underlined the idea that the association of SS and EN is more frequent than reported previously. We agree with Wasson and Folzenlogen that it is indispensable to make a histopathological confirmation of nodular lesions in patients with SS because these nodular lesions can reflect as much an EN as a neutrophilic panniculitis resulted from the spread of overlying dermal infiltrate. Other debated question is the significance of the occurrence of nodular lesions without typical SS because they can reflect both a subcutaneous SS (isolated neutrophilic panniculitis) and any other type of pannicultis with neutrophilic infiltrates [3, 10, 11]. In conclusion, the relationship between SS and EN is supported by four features: (1) the two conditions are reactive dermatoses to similar stimulus, (2) the clinical picture of both dermatoses can be similar when it is located on the legs, (3) the two conditions can appear simultaneously or sequentially in the same patient and (4) both respond to the same treatments. If we also consider that many EN have a septal neutrophilic infiltrate in the early stage, it is not a misbegotten idea that EN can be included within the group of neutrophilic dermatoses.

Behçet's Syndrome with Pyoderma‐Gangrenosum‐Like Lesions Treated Successfully with Dapsone Monotherapy

Behçet's syndrome (BS) is a rare multisystem disorder belonging to a group of neutrophilic dermatoses. We report a 65-year-old male patient who had suffered from recurrent painful orogenital ulcers for 50 years from the age of 15 and started developing pustular and bullous lesions evolving into non-healing ulcers similar to those seen in pyoderma gangrenosum (PG) two months prior to presenting to us. There was no evidence of systemic disease or malignancy. Routine baseline investigations were within normal limits. The patient was treated successfully with dapsone, antibiotics, and local wound care.